SALL1 regulates commitment of odontoblast lineages by interacting with RUNX2 to remodel open chromatin regions.

Yuxiu Lin, Yao Xiao, ChuJiao Lin, Qian Zhang, Shu Zhang, Fei Pei, Huan Liu, Zhi Chen

Stem cells (Dayton, Ohio) 2021 Feb

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Mouse dental papilla cells (mDPCs) derive from cranial neural crest cells and maintain mesenchymal stem cell characteristics. The differentiation of neural crest cells into odontoblasts is orchestrated by transcription factors regulating the expression of genes whose enhancers are initially inaccessible. However, the identity of the transcription factors driving the emergence of odontoblast lineages remains elusive. In this study, we identified SALL1, a transcription factor that was particularly expressed in preodontoblasts, polarizing odontoblasts, and secretory odontoblasts in vivo. Knockdown of Sall1 in mDPCs inhibited their odontoblastic differentiation. In order to identify the regulatory network of Sall1, RNA sequencing and an assay for transposase-accessible chromatin with high-throughput sequencing were performed to analyze the genome-wide direct regulatory targets of SALL1. We found that inhibition of Sall1 expression could decrease the accessibility of some chromatin regions associated with odontoblast lineages at embryonic day 16.5, whereas these regions remained unaffected at postnatal day 0.5, suggesting that SALL1 regulates the fate of mDPCs by remodeling open chromatin regions at the early bell stage. Specifically, we found that SALL1 could directly increase the accessibility of cis-regulatory elements near Tgf-β2 and within the Runx2 locus. Moreover, coimmunoprecipitation and proximal ligation assays showed that SALL1 could establish functional interactions with RUNX2. Taken together, our results demonstrated that SALL1 positively regulates the commitment of odontoblast lineages by interacting with RUNX2 and directly activating Tgf-β2 at an early stage. © 2020 AlphaMed Press.

Citation

Yuxiu Lin, Yao Xiao, ChuJiao Lin, Qian Zhang, Shu Zhang, Fei Pei, Huan Liu, Zhi Chen. SALL1 regulates commitment of odontoblast lineages by interacting with RUNX2 to remodel open chromatin regions. Stem cells (Dayton, Ohio). 2021 Feb;39(2):196-209